# Effects of Methandienone on the ovaries of rabbits in relation to the aromatase gene (CYP19A1) and oxidative markers and the possible protective role of selenium

**Authors:** Mohammed Ali Shahooth, Maysam Abdulrahman Ghazi, Sabea Khamees Abed, Ahmed Emad Abood, Mustafa A. Saud, Luke M Pelton, Sabea Abed, Aamir Maqtoof Abed Al-Ghareebawi

PMC · DOI: 10.12688/f1000research.174480.1 · 2026-01-24

## TL;DR

This study shows that methandienone harms rabbit ovaries by reducing estrogen and increasing oxidative stress, but selenium can help reduce these effects.

## Contribution

The novel finding is that selenium supplementation can mitigate methandienone-induced ovarian dysfunction and oxidative stress in rabbits.

## Key findings

- Methandienone significantly reduced CYP19A1 gene expression and serum estrogen levels in rabbits.
- Selenium supplementation reversed these effects and reduced oxidative stress markers like MDA and PCC.
- Combined methandienone and selenium treatment showed intermediate oxidative stress levels compared to individual treatments.

## Abstract

Anabolic-androgenic steroids (AAS), such as methandienone, are synthetic testosterone derivatives that are widely used for the enhancement of physical performance and the growth of muscles. This study looked at the effect of methandienone on ovarian CYP19A1 gene expression and oxidative status in rabbits. The work also examined whether supplementation with selenium could reduce the adverse effects caused by methandienone.

Twenty healthy adult female rabbits were randomly assigned to four groups and maintained under uniform management for 30 days. The groups included a control, a methandienone-treated group (T1), a selenium group (T2), and a combined methandienone plus selenium group (T3). Serum oestrogens concentrations were measured using standard biochemical techniques. CYP19A1 mRNA expression in ovarian tissue and markers were quantified by established molecular and biochemical protocols.

Rabbits receiving methandienone alone (T1) showed a significant decline (P≤0.05) in CYP19A1 mRNA expression and serum oestrogens when compared with the control and other treatment groups. Selenium supplementation (T2) produced marked increases in both parameters relative to G1 and G3, indicating a robust corrective effect. Oxidative stress analysis revealed elevated levels of malondialdehyde (MDA) and protein carbonyl content (PCC) in the T1 group, consistent with increased oxidative stress. Intermediate oxidative stress values were observed in the T3 group, exceeding those in the T1 group but remaining below those in the T2 group.

Methandienone appears to impair ovarian function by suppressing CYP19A1gene expression and promoting oxidative stress, leading to reduced steroidogenic activity. Selenium administration mitigates these disturbances by enhancing antioxidant defense and partially restoring gene expression and oestrogens levels. These findings highlight the potential of selenium as a supportive intervention against methandienone -induced oxidative and hormonal disruptions in rabbits.

## Linked entities

- **Genes:** CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588]
- **Chemicals:** methandienone (PubChem CID 6300), selenium (PubChem CID 6326970), malondialdehyde (PubChem CID 10964)
- **Species:** Oryctolagus cuniculus (taxon 9986)

## Full-text entities

- **Genes:** SELP (selectin P) [NCBI Gene 6403] {aka CD62, CD62P, GMP140, GRMP, LECAM3, PADGEM}, TNF-alpha [NCBI Gene 100009088], IL-6 [NCBI Gene 100008733], SELENOS (selenoprotein S) [NCBI Gene 55829] {aka AD-015, ADO15, SBBI8, SELS, SEPS1, VIMP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, Aromatase [NCBI Gene 100328545], SELENOP (selenoprotein P) [NCBI Gene 6414] {aka SELP, SEPP, SEPP1, SeP}, GAPDH [NCBI Gene 100009074], PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}
- **Diseases:** ovarian cysts (MESH:D010048), ovarian dysfunction (MESH:D010049), anemia (MESH:D000740), cytotoxicity (MESH:D064420), cardiovascular dysfunction (MESH:D002318), hormonal (MESH:C565870), infertility (MESH:D007246), follicular cysts (MESH:D005497), mitochondrial dysfunction (MESH:D028361), endocrine imbalances (MESH:D004700), metabolic disorders (MESH:D008659), anovulation (MESH:D000858), reproductive disorders (MESH:D060737), Cancer (MESH:D009369), geriatric osteoporosis (MESH:D010024), PCOS (MESH:D011085), Luke M (MESH:C566367), inflammatory (MESH:D007249)
- **Chemicals:** reactive species (-), Carbon (MESH:D002244), MDA (MESH:D008315), testosterone (MESH:D013739), lipid (MESH:D008055), ROS (MESH:D017382), estradiol (MESH:D004958), T3 (MESH:D014284), Methandienone (MESH:D008696), ATP (MESH:D000255), steroid hormone (MESH:D013256), Se (MESH:D012643)
- **Species:** Homo sapiens (human, species) [taxon 9606], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932]

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Source: https://tomesphere.com/paper/PMC12982979